Desiderio Brito
Danielle Mascarenas
Joshua Thurgood
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Venom is defined as a
poisonous matter normally
secreted by some animals
(such as snakes, scorpions, or
bees) and transmitted to prey
or an enemy chiefly by biting
or stinging; broadly: material
that is poisonous. (MerriamWebster, 2015)
Venom is generally a
compound formed by a
mixture of toxins to be used
on a broad range of targets
with various effects.
We chose to do our project on venomous snakes because during
a lecture Professor Toolson mentioned “dry bites” and this
made us realize that there is a lot we do not know about
snakes and the way they transmit their venom. As we
researched more in to the topic of snakes and snake venom
we learned the diverse mechanisms that snakes use to
distribute their venom and also how diverse the population of
venomous snakes are right here in New Mexico.
• There is a fairly large amount of debate as to the history and evolution of
snake’s ability to produce venom, but one of the leading theories is the
Toxicofera theory.
• Developed by Bryan G. Fry, the Toxicofera theory postulates that in snakes,
and other reptilian species, venom systems arose as a single novel
mutation over 100 million years ago.
• Through DNA analysis Fry discovered that a majority of the proteins and
enzymes that make up snake venom closely resemble substances found in
various other parts of snakes’ bodies. Eventually these substances became
expressed in the salivary glands and eventually were specialized to
become the venom that expresses itself today.
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Commonly known as the western
hognose snake, this snake was not
considered to be toxic until 1985
when Michael A. Morris published an
article chronicling his experience with
a bite from this snake.
Belonging to the family Colubridae
most members of this family are
nonvenomous or mostly harmless to
humans but there are a few species
whose venom can be fatal.
Colubrids envenomate their prey
using (Opistoglyphous) rear grooved
fixed fangs generally requiring
multiple bites in order to transfer a
sufficient amount of venom.
• The venom secreted from this species of snakes was
shown to contain an azocaseinase in the form of
metalloproteases which work by degrading the
extracellular matrix and coagulation proteins leading
to increased bleeding at the site of the bite and
phosphodiesterase which are believed to play a role
in the disruption of ADP- and cAMP-mediated
events.
• Metalloproteases in the body normally play a role in cell
growth and proliferation, maintenance of the extracellular
membrane, synaptogenesis, and angiogenesis. Mutant forms
of these metalloproteases can lead to over activation of cell
growth and are thought to be involved in tumor growth and
metastasis.
• Snake venom metalloproteases (SVMP) are hyperactive. They
work by degrading the extracellular matrix (especially in
endothelial cells) and lysing cell surface proteins and
coagulation proteins. This proteolytic activity results in local
lesions and hemorrhaging. Hemorrhaging can lead to delayed
muscle regeneration through inhibition of angiogenesis.
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Commonly known as the western (or
Sonoran) coral snake, these are found
in the southwestern United States
from central Arizona and
southwestern New Mexico
southward in to Mexico.
Belonging to the Elapidae family of
snakes, all members of this family are
venomous.
Elapidae feature enlarged forward
grooved fangs (proteroglyphous)
through which they inject their
venom.
• Coral snakes have a poorly
developed system for venom
delivery, requiring a chewing
action to inject the venom
much like H. nasicus.
• But the difference between
these two species is that M.
euryxanthus has teeth in the
front of the mouth used to
deliver the venom whereas H.
nasicus has teeth at the rear of
the mouth used to deliver
venom.
• Coral snake venom is primarily
neurotoxic with little local
reaction or pain at the site of
the bite.
• The net effect of the toxin is a
curare like syndrome.
• Because of their primitive
method of venom delivery
most of the bites (between 6098%) are non-envenomating.
• Approximately 4-5mg of
venom is a lethal dose to
humans.
• Several neurotoxins may be involved in combination in coral
snake venom. The venom acts postsynaptically, preventing
action potential propagation at the neuromuscular junction by
binding to ACh receptors. The venom induces central nervous
system depression, muscle paralysis, vasomotor instability,
and respiratory arrest.
• In canine victims there have been reports of the venom
causing hemolysis with severe anemia and marked
hemoglobinuria. The cause of the red blood cell destruction is
poorly understood, although it is speculated that it is because
of the effects of phospholipase A and its interaction with red
blood cell membranes.
• In the United States in 2006, Wyeth Pharmaceuticals released a statement
saying that it would no longer produce North American Coral Snake Antivenom (NACSA) which was used to treat M. fulvius (eastern coral snake)
envenomation. In lab tests on female lab rats it was shown that NACSA
was unable to treat the envenomation of M. tener (Texas Coral Snake).
• In a study to find a replacement anti-venom to be used in the United
States it was found that Coralmyn, produced by a Mexican pharmaceutical
company Bioclon, was a viable anti-venom able to treat both M. tener and
M. fulvius venom.
• M. euryxanthus is generally believed to be rather innocuous and bites tend
to be extremely rare in the species most often found in New Mexico.
NACSA
Coralmyn
• A polyclonal (secreted from
multiple cells) immunoglobulin G
(IgG) antivenom
• Inoculated in equine using M.
fulvius venom.
• Can cause adverse effects such as
anaphylaxis
• Takes up to 45 minutes to take
effect.
• ED50= 10mL neutralizes 250 LD50
doses of venom (approximately
5.5mL)
• A polyclonal fragment antigenbinding ((Fab’)2) antivenom
• Inoculated in equine using
Micururus nigrocinctus
nigrocinctus (black-banded coral
snake) venom.
• Takes effect immediately.
• ED50= 5mL neutralizes 450 LD50
doses of venom (approximately
5.5mL)
• Part of the Crotalinae (Pit Viper)
subfamily of snakes
• There are 32 known species which
are all native to the North and
South Americas
• All Rattlesnake species use hemotoxic
venom
• Uses bloodstream to destroy tissue
and to cause swelling and internal
bleeding
• Some species also use a combination of
hemotoxins and neurotoxins in their
venom
• Neurotoxins cause paralysis
• Rattlesnake species possess hinged
fangs
• They can retract these fangs when not
in use, retracting them against there
palate
• These fangs are connected via ducts
to poison glands
• This gives them better control of the
amount of venom used in a “bite”
• Rattlesnake toxins also show
geographic variance
• Crotalus scutulatus
• Crotalus atrox
• Mojave Rattlesnake
• Southwestern United States and Central
Mexico
• Uses a powerful neurotoxin in its venom
• One of the most deadly venoms in
the United States
• The neurotoxin in Crotalus Scutulatus venom is known
as Mojave Toxin
• Made up of two subunits
• A phospholipase A2
• An acidic peptide
• They are not significantly toxic alone but become
extremely toxic when together
• Crotalus Scutulatus venom attacks
the nervous system
• Venom Effects:
• Visual abnormalities
• Difficulties swallowing and
talking
• Muscle Weakness
• Difficulty breathing
• The effects of the Mojave Toxin are presynaptic
• Gated calcium channels are inhibited through
phospholipase activity
• Action Potential generation is stopped
• Causes paralysis of muscle
• Explains many effects such as muscle
weakness, difficulties breathing, etc.
• Treatment for the envenomation
by the Mojave Rattlesnake is the
use of antivenom
• CroFab antivenom is used
specifically
• Crofab uses Mojave
Rattlesnake venom so it is
used almost uniformly to
treat rattlesnake bites
• Western Diamondback Rattlesnake
• Found across most of the Southern United
States and Northern Mexico
• Mixture of toxins in venom, but primarily
hemotoxic
• Also contains some myotoxins and
cytotoxins
• Crotolus Atrox venom contains
many proteolytic enzymes
• These break done proteins
including structural proteins
• Leads to tissue damage and
death
• Also contains zinc
metalloproteinases
• Hemorrhagic component
• A protein that coordinates with
zinc ions
• Also reduces skeletal muscle
regeneration
• Local Effects
• Pain
• Internal Bleeding
• Swelling
• Muscle Damage
• Bruising
• Tissue Death
• Systemic Effects
• Headache
• Nausea
• Vomiting
• Abdominal Pain
• Diarrhea
• Dizziness
• Most damage done by
Crotolus Atrox venom is
due to hemorrhaging
• The action of metal ions
coordinating with
proteins
(metalloproteinases)
causes severe bleeding
and tissue damage
• Treatment of Crotolus Atrox envenomation is also the use of the antivenom
CroFab
• Crofab is made from the toxins of several snakes from the subfamily
Crotalinae
• Counteracts the effects of envenomation of many rattlesnake species
• What is it: Snake Venom
• Where it comes from: Mutated salivary glands
• What it does: There are a number of different toxins
that come in to play across the different species of
snakes. They generally show hemotoxic and
neurotoxic effects leading to swelling at the bite site
and increased bleeding (hemotoxic effect) and in
some more powerful venoms they can cause
paralysis (neurotoxic effect) and even death.
• How it is delivered: depending on the family that the
snake belongs to will tell you a lot about how snakes
envenomate their prey.
– Colubrids have fixed fangs in the back of the mouth with
long venom glands that run below the teeth, but often the
venom is rather weak.
– Elapids have fixed fangs in the front of the mouth and large
venom glands above the fangs.
– Crotalus have hinged fangs that they can control and this
muscular control of the fangs makes them better at
controlling how much venom they release in their bites.
Generally members of this family have very powerful
venom.
• Antivenoms are generally created from the venom that they
are meant to treat.
• The development of complex venom distribution systems
have made snakes excellent hunters that are to be taken with
caution at all times.
• Snake venom is a very diverse subject as snakes vary greatly in
what they use venom for. Uses range from offensive use to
hunt prey, defensive uses to warn predators that they are
dangerous, and predigestion of prey.
– It should be noted that Western Diamondback venom
causes tissue necrosis but it is not used in predigestion of
its prey.
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Biardi, J. E., and Coss, R.G. 2011. Rock Squirrel (Spermophilus Variegatus) Blood Sera
Affects Proteolytic and Hemolytic Activities of Rattlesnake Venoms. Toxicon. Vol. 57, No.
2: 323-31.
Borkow, G., Marco, D., Ovadia, M. 2008. Isolation and Partial Characterization of an
Antiviral Proteolytic Fraction from the Venom of Echis Carinatus Sochureki. The Open
Biology Journal. Vol. 1: 21-26.
Cameron, J. The danger of scorpion sting. Retrieved April 8, 2015 from
http://www.thecameronteam.com/the-danger-of-scorpion-sting/.
Carstairs, SD, AA Kreshak, and DA Tanen. 2013. Crotaline Fab Antivenom Reverses Platelet
Dysfunction Induced by Crotalus Scutulatus Venom: an in Vitro Study. Academic
Emergency Medicine: Official Journal of the Society for Academic Emergency Medicine.
Vol. 20, No. 5: 522-5.
Chang, C., and Werb, Z. The Many Faces of Metalloproteases: Cell Growth, Invasion,
Angiogenesis and Metastasis. Trends in Cell Biology. U.S. National Library of Medicine.
Dagda, R.K, B Zhang, W Welch, S.E Gasanov, S.E Gasanov, W Welch, and E.D Rael. 2014.
Molecular Models of the Mojave Rattlesnake (crotalus Scutulatus Scutulatus) Venom
Metalloproteinases Reveal a Structural Basis for Differences in Hemorrhagic Activities.
Journal of Biological Physics. Vol. 40, No. 2: 193-216.
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Fox, Jay W, and Jon B. Bjarnason. 1983. New Proteases from Crotalus Atrox Venom. Toxin
Reviews. Vol. 2 No. 2: 161-204
Fox, JW, R Campbell, L Beggerly, and JB Bjarnason. 1986. Substrate Specificities and Inhibition
of Two Hemorrhagic Zinc Proteases Ht-C and Ht-D from Crotalus Atrox Venom. European
Journal of Biochemistry / Febs. Vol. 156, No. 1: 65-72.
Fry, B.G., Vidal, N., van der Weerd, L., Kochva, E., Renjifo, C. 2009. Evolution and
diversification of the Toxicofera reptile venom system. Journal of Proteomics. Vol. 72, No. 2:
127-136.
Fry, B.G., Casewell, N.R., Wuster, W., Vidal, N., Young, B., Jackson, T.N.W. 2012. The structural
and functional diversification of the Toxicofera reptile venom system. Toxicon. Vol. 60, No. 4:
434-448.
Gray, R. Bee sting venom could provide treatment for arthritis. Retrieved April 8, 2015 from
http://www.telegraph.co.uk/news/science/science-news/7856017/Bee-sting-venom-couldprovide-treatment-for-arthritis.html.
Hill, R.E., Mackessy, S.P. 2000. Characterization of venom (Duvernoy’s secretion) from twelve
species of colubrid snakes and partial sequence of four venom proteins. Toxicon. Vol. 38, No.
12: 1663-1687.
Peterson, M. E. 2006. Snake Bite: Coral Snakes. Clinical Techniques in Small Animal Practice.
Vol. 21, No. 4: 183-86.
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Ramos, O.H.P, and H.S. Selistre-De-Araujo. 2006. Snake Venom Metalloproteases — Structure
and Function of Catalytic and Disintegrin Domains. Comparative Biochemistry and Physiology
Part C: Toxicology & Pharmacology. Vol. 142, No. 3-4: 328-46.
Sánchez, E. E., Lopez-Johnston, J.C., Rodríguez-Acosta, A., and Pérez, J.C. 2008. Neutralization
of Two North American Coral Snake Venoms with United States and Mexican Antivenoms.
Toxicon Vol. 51, No. 2: 297-303.
Wassif, C., Cheek, D., Belas, R. 1995. Molecular Analysis of a Metalloprotease from Proteus
mirabili. Journal of Bacteriology. Vol. 177, No. 20: 5790-5798.
http://bib.ge/reptiles/open.php?id=1660
http://www.dailymail.co.uk/news/article-2344107/Boy-11-bitten-eastern-diamondbackrattlesnake-survives-given-record-EIGHTY-vials-anti-venom.html
http://www.madrean.org/symbfauna/imagelib/photographers.php?phuid=28&imgcnt=182&l
start=100&lnum=100
http://www.popsci.com/scitech/article/2008-03/evolution%E2%80%99s-most-effectivekiller-snake-venom